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Monocyte matrix metalloproteinase production in Type 2 diabetes and controls--a cross sectional study
Mark D Baugh1, Jelena Gavrilovic, Isabel R Davies
1Bertram Diabetes Research Unit, Norfolk and Norwich University Hospital NHS Trust, Norwich NR4 7UY, UK. mark.baugh@uea.ac.uk
Background:
Coronary plaque rupture may result from localised over expression of matrix metalloproteinases (MMPs) within the plaque by infiltrating monocyte-macrophages. As MMP expression can be promoted by the modified lipoproteins, oxidative stress and hyperglycaemia that characterises Type 2 diabetes, we hypothesised that peripheral monocytes in these patients, exposed to these factors in vivo, would demonstrate increased MMP production compared to controls.
Methods:
We examined peripheral venous monocyte expression of MMP and tissue inhibitor of metalloproteinase-1 (TIMP-1) in 18 controls and 22 subjects with Type 2 diabetes and no previous cardiovascular complications.
Results:
No significant difference in MMP-1, 3 or 9 or TIMP-1 production was observed between control and diabetes groups.
Conclusions:
Monocyte MMP-1, 3, and 9, and TIMP-1, production are not abnormal in Type 2 diabetes. This data cannot be extrapolated to monocyte-macrophage behaviour in the vessel wall, but it does suggest MMP and TIMP-1 expression prior to monocyte infiltration and transformation are not abnormal in Type 2 diabetes.
Insights
Peripheral monocytes in Type 2 diabetes patients do not show increased matrix metalloproteinase (MMP) or tissue inhibitor of metalloproteinase-1 (TIMP-1) production compared to controls, suggesting normal expression prior to vessel wall infiltration.
Area of Science:
- Cardiovascular Research
- Diabetes Mellitus
- Immunology
Background:
- Coronary plaque rupture is linked to matrix metalloproteinases (MMPs) overexpressed by monocyte-macrophages.
- Type 2 diabetes features modified lipoproteins, oxidative stress, and hyperglycemia, which can promote MMP expression.
Purpose of the Study:
- To investigate if peripheral monocytes in Type 2 diabetes patients exhibit increased MMP and TIMP-1 production compared to healthy controls.
- To assess the role of in vivo factors in Type 2 diabetes on monocyte MMP production.
Main Methods:
- Examined peripheral venous monocyte expression of MMPs (MMP-1, 3, 9) and TIMP-1.
- Compared expression levels between 22 Type 2 diabetes subjects (no prior cardiovascular complications) and 18 controls.
Main Results:
- No significant differences were found in the production of MMP-1, MMP-3, MMP-9, or TIMP-1 between the Type 2 diabetes group and the control group.
- Monocyte MMP and TIMP-1 production levels were comparable in both groups.
Conclusions:
- Monocyte MMP-1, 3, and 9, and TIMP-1 production are not abnormal in Type 2 diabetes.
- This suggests that MMP and TIMP-1 expression before monocyte infiltration into the vessel wall is not altered in Type 2 diabetes.